3KZF

Structure of Giardia Carbamate Kinase

Summary for 3KZF

• Entry DOI: 10.2210/pdb3kzf/pdb
• Descriptor: Carbamate kinase, GLYCEROL (2 entities in total)
• Functional Keywords: carbamate kinase, arginine dihydrolase pathway, giardia lamblia, drug target, kinase, transferase
• Biological source: Giardia lamblia ATCC 50803
• Total number of polymer chains: 4
• Total formula weight: 136269.25

Authors

Galkin, A.,Herzberg, O. (deposition date: 2009-12-08, release date: 2010-04-07, Last modification date: 2023-09-06)

Primary citation

Galkin, A.,Kulakova, L.,Wu, R.,Nash, T.E.,Dunaway-Mariano, D.,Herzberg, O.
X-ray structure and characterization of carbamate kinase from the human parasite Giardia lamblia.
Acta Crystallogr.,Sect.F, 66:386-390, 2010

PubMed Abstract: Carbamate kinase catalyzes the reversible conversion of carbamoyl phosphate and ADP to ATP and ammonium carbamate, which is hydrolyzed to ammonia and carbonate. The three-dimensional structure of carbamate kinase from the human parasite Giardia lamblia (glCK) has been determined at 3 A resolution. The crystals belonged to the monoclinic space group P2(1), with unit-cell parameters a = 69.77, b = 85.41, c = 102.1 A, beta = 106.8 degrees . The structure was refined to a final R factor of 0.227. The essentiality of glCK together with its absence in humans makes the enzyme an attractive candidate for anti-Giardia drug development. Steady-state kinetic rate constants have been determined. The k(cat) for ATP formation is 319 +/- 9 s(-1). The K(m) values for carbamoyl phosphate and ADP are 85 +/- 6 and 70 +/- 5 microM, respectively. The structure suggests that three invariant lysine residues (Lys131, Lys216 and Lys278) may be involved in the binding of substrates and phosphoryl transfer. The structure of glCK reveals that a glycerol molecule binds in the likely carbamoyl phosphate-binding site.

PubMed: 20383005
DOI: 10.1107/S1744309110004665

Experimental method

X-RAY DIFFRACTION (3 Å)